The gram-negative bacterium Helicobacter pylori is an important human pathogen, involved in several gastroduodenal diseases. Colonization of gastric epithelium by the bacterium leads to active inflammation and progressive chronic gastritis, with a greatly enhanced risk of progression to peptic ulcer disease.
In order to colonize the gastric mucosa, H. pylori uses a number of virulence factors. Such virulence factors comprise several adhesins, with which the bacterium associates with the mucus and/or binds to epithelial cells; ureases which helps to neutralize the acid environment; and proteolytic enzymes which makes the mucus more fluid.
Despite a strong apparent host immune response to H. pylori, with production of both local (mucosal) as well as systemic antibodies, the pathogen persists in the gastric mucosa, normally for the life of the host. The reason for this is probably that the spontaneously induced immune-response is inadequate or directed towards the wrong epitopes of the antigens.
In order to understand the pathogenesis and immunology of H. pylori infections, it is of great importance to define the antigenic structure of this bacterium. In particular, there is a need for characterization of surface-exposed like adhesins) and secreted proteins which, in many bacterial pathogens, have been shown to constitute the main virulence factors, and which can be useful for the diagnosis of H. Pylori and in the manufacture of vaccine compositions.
Cloning of the gene hpaA, which codes for a 20 kDa receptor-binding subunit of the N-acteylneuraminyllactose-binding fibrillar hemagglutinin (NLBH) of H. pylori, has been disclosed by Evans et al. (1993) J. Bacteriol. 175, 674-683.
Monoclonal antibodies (MAbs) against membrane preparations of H. pylori have been disclosed by Bolin et al. (1995) J. Clin. Microbiol. 33, 381-384. One of these MAbs, designated HP30-1:1:6, reacted with a 30 kDa protein which was shown to be exposed on the surface of intact bacteria and to have properties like that of an adhesin.
Whenever stressed or threatened, the H. pylori cell transforms from a bacillary to a coccoid form. In the coccoid form, the H. pylori cell is much less sensitive to antibiotics and other anti-bacterial agents. Circumstantial evidence indicate the H. pylori might be transmitted between individuals in this form, possibly via water or direct contact. An efficient vaccine composition should therefore elicit an immune response towards both the coccoid and the bacillary form of H. pylori. Since systemic immunity probably only plays a limited role in protection against mucosal infections, it is also important that the vaccine composition will enhance protective immune mechanisms locally in the stomach.